Currently no an effective vaccine or cure for HIV/AIDS, the only treatment option is to suppress viral replication with antiretroviral therapy on a lifelong basis.
Although lots of drugs have been invented and used effectively to fight against HIV virus by employing a combinational use of nucleoside/nucleotide reverse transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitors, and/or protease inhibitors, which are targeted at different stage of HIV virus life cycle, it has also brought out the side effects at same time. Among them, the most serious one is the multidrug-resistant viral strains evolved. Even with the new therapies available like fusion, entry, and integrase in recent years, the new resistant viral strains have also been reported both in vitro and in vivo. Therefore there is an urgent need to have a drug with a novel mechanism which may help to address increasing problems of current therapies.
Maturation is an essential step in the life-cycle of HIV-1. It is the transition of the immature, non-infectious virus particle to the mature and infectious virion which represents as an excellent target for development of new class of anti-HIV-1 drugs.
Some derivatives of lupane triterpenoid have been reported to have anti-HIV-1 activity, they bind to the preproteins (Gag) that specifically block HIV-1 protease to cleave p25 (CA-SPI) protein into their functional active form p24 (CA), resulting in the accumulation of the p25 (CA-SPI), immature and noninfectious HIV-1 virions that may prevent the subsequent cycles of HIV infection. These pharmacologically active lupane triterpenoid derivatives are called maturation inhibitors (MI), which represent a novel mechanism in fighting against HIV virus and may provide a new treatment for HIV with resistance to current therapies. Currently there is no such approval drug on the market based on this mechanism.
Bevirimat (PA-457) is a new experimental agent to inhibit this last step of p25 (CA-SPI) protein being converted into the functional form p24 (CA). It has been reported that Bevirimat can reduce ART-resistant strains and wide type HIV viral load in patients, and has demonstrated synergy with antiretrovirals from all classes, but patients with Gag polymorphisms at Q369, V370, or T371 are resistant to this agent's therapy.